In the brains of patients with Alzheimer's disease, peptides each consisting of approximately 40 amino acids, called amyloid β proteins, which widely accumulate outside neurons to form insoluble plaques (senile plaques) are observed. These senile plaques are considered to kill neurons and cause the onset of Alzheimer's disease, and therefore, agents promoting degradation of amyloid β proteins and amyloid β vaccines have been studied as therapeutic agents for Alzheimer's disease.
Secretases are enzymes which cleave a protein called amyloid precursor protein (APP) within a cell and generate an amyloid β protein. An enzyme which produces N-terminals of amyloid β proteins is called as BACE1 (beta-site APP-cleaving enzyme 1, BACE1). It is considered that production of amyloid β proteins may be suppressed by inhibiting this enzyme, and thus a substance with such an effect can serve as a therapeutic agent for Alzheimer's disease.
Patent Documents 1 and 8 to 19 disclose BACE 1 inhibitors but each of them has a structure different from those of the compounds of the present invention.
Patent Documents 2 to 7 and Non-Patent Documents 1 to 3 disclose compounds having a structure similar to those of the compounds of the present invention have NOS inhibitory activity, HSP90 inhibitory activity or melanocortin 4 receptor binding activity.